Epalrestat, (5-[(1Z,2E)-2-methyl-3-phenylpropenylidene]-4-oxo-2-thioxo-3-thiazolidineacetic acid), shown below, is an aldose reductase inhibitor. The preparation and pharmacologic activity of epalrestat is described in U.S. Pat. No. 4,831,045. Epalrestat has previously been described as useful for treating various conditions, including diabetes and diabetic complications, as well as affording cardioprotection in non-diabetic patients.

Epalrestat has a positive indication for the treatment of diabetic neuropathy, and has been reported as useful for the treatment of other diabetic complications including, for example, diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic gastroparesis, diabetic microangiopathy, and diabetic macroangiopathy in mammals.
Epalrestat is also useful in affording cardioprotection to subjects who may not be suffering from diabetes, and as a neuroprotectant or treatment for neurological or neurodegenerative disorders. Therapeutic activity of epalrestat in various conditions has been demonstrated in the clinical literature. For example, see Machii H. et al. (1996). Gendai Iryo, v. 28, p. 1273; Miyamoto S. et al. (1986). Gendai Iryo, v. 18 (Extra Issue HI), p. 82; Goto Y. et al. (1990). Journal of Clinical and Experimental Medicine, v. 152, p. 405; Nakano K. et al. (1990). Journal of Clinical and Experimental Medicine, v. 152, p. 137; Okamoto H. et al. (2003). Internal Medicine, v. 42, pp. 655-664; Hamada Y. et al. (2000). Diabetes Care, v. 23, pp. 1539-44.; Goto Y. et al. (1993). Diabet Med, v. 10(suppl 2), pp. S39-43; Goto Y. et al. (1995). Biomed Pharmacother, v. 49, pp. 269-277; Uchida K. et al. (1995). Clin Ther, v. 17, pp. 460-466; Hotta N. et al. (1996). J Diabetes Complications, v. 10, pp. 168-172; Hotta N. et al. (2006). Diabetes Care, v. 29, pp. 1538-1544; Matsuoka K. et al. (2007). Diabetes Res Clin Pract, v. 77(suppl 1), pp. S263-268; Nakayama M. et al. (2001). Diabetes Care, v. 24, pp. 1093-1098; Baba M. (2003). Journal of the Peripheral Nervous System, v. 8, p. 170; Yasuda H. et al. (2000). Diabetes Care, v. 23, p. 705; IkedaT et al. (1999). Diabetes Research and Clinical Practice, v. 43, pp. 193-198; Katayama M. et al. (1995). Electroencephalography and Clinical Neurophysiology/Electromyography and Motor Control, v. 97, p. 81; and Misawa S. et al. (1996). Neurology, v. 66, pp. 1545-1549.